SACCHAROMYCES-CEREVISIAE PMS2 MUTATIONS ARE ALLELES OF MLH1, AND PMS2-2 CORRESPONDS TO A HEREDITARY NONPOLYPOSIS COLORECTAL CARCINOMA-CAUSING MISSENSE MUTATION

A number of mutant Saccharomyces cerevisiae strains having phenotypes consistent with defects in DNA mismatch repair have been described, bu t not all have been extensively characterized. In this study we demons trated that the pms2-1 and pms2-2 alleles arise from missense mutation s in the MLH1 gene which inactivate MLH1. One of these alleles, pms2-2 , causes the same amino acid substitution in a highly conserved region of the known MutL homologs as that caused by a proposed missense muta tion observed in a Swedish hereditary nonpolyposis colorectal carcinom a kindred. This observation supports the functional significance of mi ssense mutations found in hereditary nonpolyposis colorectal carcinoma kindreds and indicates that in some cases S. cerevisiae can serve as a useful model system for the analysis of such mutations.